Long term survival of hypoplastic left heart syndrome infants: Meta-analysis comparing outcomes from the modified Blalock–Taussig shunt and the right ventricle to pulmonary artery shunt

doi:10.1016/j.ijcard.2017.10.040

International Journal of Cardiology

Volume 254, 1 March 2018, Pages 107-116

https://doi.org/10.1016/j.ijcard.2017.10.040 Get rights and content

Abstract

Background

Stage 1 palliation of hypoplastic left heart syndrome (HLHS) involves the Norwood procedure combined with a modified Blalock–Taussig shunt (mBTS) or right ventricle to pulmonary artery shunt (RVPAS). Short-term survival has been described previously, whereas longer-term outcomes remain a subject of debate. This meta-analysis aimed to describe the short and long-term survival outcomes of these two shunts, and explore factors that might influence survival.

Methods

Medline, Cochrane Libraries and EMBASE were systematically searched, and 32 studies were included for statistical synthesis, comprising 1348 mBTS and 1258 RVPAS patients.

Results

While early in-hospital survival was superior in the RVPAS group (RR = 1.5, p < 0.05, 95% CI: 1.21–1.85), this difference was lost from 2 years post-stage 1 palliation (RR = 0.91, p > 0.05, 95% CI: 0.79–1.04), and maintained unchanged up to 6 years. This shift in survival was also reflected in inter-stage survival, with superior RVPAS outcomes between stage 1 and 2 (RR = 1.62, p < 0.05, 95% CI: 1.39–1.88), and equivalent outcomes between stage 2 and 3. Potential contributors to this included a significantly higher rate of pulmonary artery stenosis in the RVPAS group and an increased requirement for shunt re-intervention in this group prior to stage 2.

Conclusions

Despite early advantages, RVPAS and mBTS for palliation of hypoplastic left heart syndrome produced comparable long-term survival. The RVPAS patients experienced more pulmonary artery stenosis and requirement for shunt re-intervention. The impact of shunt type on quality and survival with a Fontan is yet to be assessed.

Introduction

Modified Blalock–Taussig Shunt (mBTS) and right ventricle to pulmonary artery shunt (RVPAS) provide pulmonary blood as part of stage 1 procedure (S1P) for hypoplastic left heart syndrome (HLHS). In mBTS, the conduit connects the subclavian to the pulmonary artery, whereas in the RVPAS, the conduit connects the right ventricle to the pulmonary artery. Initial experience with the mBTS was associated with relatively high early (25–40%) and inter-stage (prior to stage palliation, S2P) (30–50%) [1], [2], [3], [4] mortality. This was primarily attributed to coronary insufficiency which was thought to be related to the diastolic run-off into the pulmonary circulation, inherent to the continuous flow nature of the shunt. Consequently, the RVPAS technique was created by Sano et al. as an alternative to the mBTS [5]. As there is no pulmonary blood flow during diastole, this shunt eliminates diastolic run-off, thus lowering the risk of myocardial ischaemia due to insufficient coronary blood flow. Subsequent retrospective cohort studies demonstrated improved early and inter-stage survival with RVPAS [6], [7], [8], [9], [10], as well as improved growth of the pulmonary arteries prior to S2P [11], [12]. Furthermore, the Single Ventricle Repair Trial (SVR), a landmark randomised controlled trial comparing the two shunts, demonstrated superior transplant-free survival at 1 year for the RVPAS (74% survival for RVPAS group; 64% survival for mBTS group) [8]. In contrast, a meta-analysis by Sharma et al. did not demonstrate any significant differences in early survival even after controlling for the era of operation, which may have influenced the choice of shunt [13]. However, due to duplicate bias from usage of 4 studies deriving data from medium sized overlapping cohorts (Tabbut et al. [14] and Ballweg et al. [15]; Fischbach et al. [16] and Photiadis et al. [17]), results may be skewed from the true effect size.

With further follow up of these patients, new data are emerging regarding the longer term outcomes of both strategies. Recent studies have demonstrated an increased rate of atrioventricular valve regurgitation and right ventricular dysfunction in the RVPAS patients at stage 3 palliation (S3P) and during long-term follow up [12], [18], [19]. However, long-term survival remains a topic of debate. Several single centre studies [12], [15], [20] and the SVR data [21] found comparable survival at 3–6 year follow up, whereas the Congenital Heart Surgeons' Society study [22] suggested superior transplant free survival of the RVPAS patients at 6 years, even though the authors noted convergence of survival curves with increasing follow up.

Therefore, the current study aims to compare outcomes after an initial surgical strategy involving a mBTS versus a RVPAS for palliation of HLHS patients. Firstly, recognising duplicate bias in previous meta-analyses, we aim to produce a more rigorous and contemporary evaluation of early and inter-stage mortality. Secondly, we aim to synthesise all available data on long-term survival and non-survival outcomes of both shunt types. Based on current available evidence, it is hypothesised that RVPAS will be associated with an early advantage, which will be lost in longer follow-up. Knowledge of such outcomes will be useful in guiding the choice of shunt strategy in clinical practice.

Section snippets

Literature search strategy

We followed recommended guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [23], [24]. Electronic searches were performed on 30th April 2017 using Medline, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systemic Reviews. To achieve the maximum sensitivity of the search strategy, the terms “hypoplastic” OR “left heart syndrome” AND “Norwood” OR “Sano” OR “Blalock” OR “pulmonary artery shunt” OR “BTS” OR “RVPA” were

Quality assessment

The results of the search are shown in Fig. 1 as according to the PRISMA flow chart (Fig. 1). A total of 32 studies were selected for statistical synthesis including seven RCTs [8], [19], [21], [28], [29], [30], [31] and 25 retrospective cohort studies [6], [9], [10], [11], [12], [15], [16], [18], [20], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47]. Of the RCTs, six were derived from the SVR and the data was thus collated accordingly without

Discussion

The mBTS and RVPAS are important means to provide pulmonary flow in S1P of HLHS. However, due to the relatively recent re-invention of the RVPAS technique, the longer-term outcomes of these patients continue to be questioned. The current meta-analysis demonstrated, using long-term follow up data of up to 6 years, that despite early survival advantages of the RVPAS, there is a gradual equalisation of survival from 2 years post S1P. This is corroborated by our analysis of inter-stage survival,

Author contributions

All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

Grants

The authors received no financial support for the research, authorship, and/or publication of this article.

Conflict of interest

The authors report no relationships that could be construed as a conflict of interest.

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Observational studies have demonstrated an association between the use of digoxin and reduced interstage mortality after Norwood operation for hypoplastic left heart syndrome (HLHS). Digoxin use has increased significantly but remains variable between different hospitals, independent of case-mix. Instrumental variable analyses have the potential to overcome unmeasured confounding, the major limitation of previous observational studies and to generate an estimate of the attributable benefit of treatment with digoxin.
A cohort of neonates with HLHS born from January 1, 2007 to December 31, 2021 who underwent Norwood operation at Pediatric Health Information Systems Database hospitals and survived >14 days after operation were studied. Using hospital-specific, 6-month likelihood of administering digoxin as an instrumental variable, analyses adjusting for both unmeasured confounding (using the instrumental variable) and measured confounders with multivariable logistic regression were performed.
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Infants with hypoplastic left heart syndrome (HLHS) or similar single ventricle cardiac lesions require a three-stage surgical approach, the first step being the Stage I Norwood procedure. The Queensland Children’s Hospital (QCH) in Australia is a tertiary hospital providing the only cardiac surgical service to children in Queensland and northern New South Wales.
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We retrospectively evaluated all infants undergoing the stage I Norwood procedure between January 2015 and August 2021. Mortality, intensive care length of stay, events of cardiac arrest following surgery and duration of mechanical ventilation were calculated and analysed for subgroups depending on type of pulmonary shunt type (right-ventricle-to-pulmonary-artery shunt [RVPAS] vs the modified Blalock-Taussig shunt [MBTS]).
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In total, 303 participants (55% of the SVR cohort) from 9 of 15 sites were studied (48% MBTTS). Observed total costs at 1 year were lower for MBTTS ($701,260 ± 442,081) than those for RVPAS ($804,062 ± 615,068), a difference that was not statistically significant (P = 0.10). Total costs were also not significantly different at 3 and 5 years (P = 0.21 and 0.32). Similarly, cost-per-day-alive did not differ significantly for either group at 1, 3, and 5 years (all P > 0.05). In analyses of transplant-free survivors, total costs and cost-per-day-alive were higher for RVPAS at 1 year (P = 0.05 for both) but not at 3 and 5 years (P > 0.05 for all). In multivariable models, aortic atresia and prematurity were associated with increased cost-per-day-alive across follow-up (P < 0.05).
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Single ventricle patients undergoing S1P between July 2004 and October 2018 at a single institution were included. Patients having one or more HR factors were considered to have HR status, with all others classified as low risk (LR). Longitudinal survival stratified by risk status was compared after each palliative stage, in addition to readmission and length of stay. Proportional hazards modeling was used to determine risk factors for longitudinal mortality.
Of 132 patients presenting during the study for S1P, 57 (43.2%) were classified as HR. Overall 10-year survival was decreased in the HR cohort (P = .001). The HR patients were at significantly increased risk of death during interstage I (P = .01) and interstage II (P = .01), but survival was similar to that of LR patients after S3P (P = .31). Readmission rates after S2P were higher among HR patients (41.9% vs 22.5%, P = .029), but were similar after S3P. Length of stay was increased in the HR cohort after S2P (median 11 vs 9 days, P = .024) but similar to the LR group after S3P. Prematurity was the risk factor most consistently associated with increased mortality after all stages.
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2019, Anales de Pediatria
Desde que Norwood et al. efectuaron la primera paliación exitosa en 1983, ha habido cambios sustanciales en el diagnóstico, el manejo y el pronóstico del síndrome de corazón izquierdo hipoplásico. La supervivencia en el estadio i de la paliación quirúrgica ha aumentado hasta el 90% en muchas instituciones, con la posibilidad de sobrevivir hasta la vida adulta. No obstante, la morbimortalidad asociada continúa siendo sustancial.
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Since the first successful palliation was performed by Norwood et al. in 1983, there have been substantial changes in diagnosis, management, and outcomes of hypoplastic left heart syndrome, Survival for stage 1 palliation has increased to 90% in many centres, with patients potentially surviving into adulthood. However, the associated morbidity and mortality remain substantial.
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